TakeAim Lymphoma data for the combination of emavusertib plus ibrutinib show tumor reduction in 8 of 9 evaluable patients, including 2 complete responses and 2 partial responses

Potential for overcoming ibrutinib resistance demonstrated with a complete response in a patient who had prior treatment with ibrutinib

TakeAim Leukemia data, top-line data previously released in January, highlight emavusertib’s single-agent activity in heavily pretreated AML and HR-MDS patients

LEXINGTON, Mass.


,


June 4, 2022


/PRNewswire/ — Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, today announced the presentation of encouraging clinical data from both the TakeAim Lymphoma and TakeAim Leukemia studies at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting currently taking place in

Chicago

and online until

June 7, 2022

.

“We are excited to share data with the oncology community from our TakeAim Lymphoma and TakeAim Leukemia studies at ASCO, including the first release of clinical data investigating the use of emavusertib in combination with ibrutinib in patients with Non-Hodgkin’s Lymphoma,” said

James Dentzer

, President and Chief Executive Officer of Curis. “These data demonstrate encouraging signs of anti-cancer activity, including a complete response in a primary CNS lymphoma patient who had prior treatment with ibrutinib. We also presented a poster with data from the TakeAim Leukemia study, previously disclosed in a

January 2022

press release, demonstrating emavusertib’s encouraging monotherapy activity in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).”

“In addition to the data from Curis’s studies, there are presentations at the meeting this year by our collaborators at

Washington University

and the

University of Florida

, which help more fully explore emavusertib’s use in tumor types outside of the company’s current focus in hematologic malignancies,” said

Robert Martell

, M.D., Ph.D., Head of Research and Development.

TakeAim Lymphoma:

The TakeAim Lymphoma study is a Phase 1/2 open-label, dose escalation, dose expansion clinical trial investigating emavusertib as monotherapy and in combination with ibrutinib in patients with R/R hematologic malignancies, such as non-

Hodgkins’s

lymphoma and other B cell malignancies. The poster presentation (#7575) made by Dr.

Grzegorz Nowakowski

, Division of Hematology, Mayo Clinic-Minnesota, today at ASCO includes clinical data from a

May 6, 2022

data cutoff, on 13 patients who received the combination, 9 of whom had post-baseline response assessments and were evaluable for response.

Key findings in patients treated with the combination included:

• The combination appeared to be well tolerated
• No dose-limiting toxicities (DLTs) at 200mg of emavusertib; 2 DLTs observed at 300mg (stomatitis and syncope)
• 8 of 9 evaluable patients experienced reduction in tumor burden, including:
• 2 complete responses (CR) (primary CNS lymphoma and mantle cell lymphoma)
• 2 partial responses (PR) (chronic lymphocytic leukemia and mantle cell lymphoma)
• One of the CRs was in a patient who had received prior treatment with ibrutinib, suggesting that the combination may be able to overcome ibrutinib resistance

Next steps for the TakeAim Lymphoma study include further dose expansion in order to determine the Recommended Phase 2 Dose for the combination.

TakeAim Leukemia:

The TakeAim Leukemia study is a Phase 1/2 dose escalation and dose expansion study examining emavusertib use as both monotherapy and in combination with azacitidine or venetoclax in patients with R/R AML or high risk MDS.  The poster presentation (#7016) made by Dr.

Guillermo Garcia-Manero

, Chief of the Section of Myelodysplastic Syndromes within the Department of Leukemia at The

University of Texas

MD Anderson Cancer Center, today at ASCO, include clinical data from a

December 16, 2021

data cutoff for the 49 patients who had been treated with emavusertib in monotherapy as of that date.

Key safety findings included:

• Emavusertib was well-tolerated across multiple dose levels, including at the Recommended Phase 2 Dose of 300 mg BID
• No dose-limiting myelosuppression observed
• No cumulative toxicities observed

These attributes of emavusertib’s emerging safety profile may provide an advantage compared to current standard of care therapies in monotherapy and may also make emavusertib an attractive candidate for addition to combination therapy regimens.

Key tumor assessment findings included:

Collaborator Studies:

• In patients with spliceosome-mutated R/R AML:
• CR/CRh rate of 40% (2 out of 5 patients) (CRh=complete response with partial hematologic recovery)
• Both patients who achieved CR/CRh have been on study > 6 months and achieved negative MRD (minimal residual disease) status
• Consistent tumor burden reduction observed, 4 out of 5 patients achieved blast reduction, 3 of whom by ≥ 50%
• In patients with spliceosome-mutated R/R MDS:
• Objective response rate of 57% (4 out of 7 patients)
• One of the patients who achieved a marrow CR (mCR) proceeded to stem cell transplant after 1 cycle
• Consistent tumor burden reduction observed, with 4 out of 6 patients with elevated baseline blast counts achieving ≥ 50% reduction in blast counts
• In patients with FLT3-mutated R/R AML:
• CR rate of 33% (1 out of 3 patients)
• 2 out of 3 patients showed eradication of FLT3 mutation following treatment, indicating potential for disease modification with emavusertib
• Consistent tumor burden reduction observed with 2 out of 3 patients with elevated blast counts achieving ≥ 50% reduction in blast counts

Being presented today (#TPS4168) is work in gastric cancer by Dr.

Kian-Huat Lim’s

team at

Washington University

School of Medicine. Based on compelling preclinical work, Dr. Lim and his team have developed a clinical study exploring combination of emavusertib (CA-4948) in combination with FOLFOX chemotherapy plus nivolumab or pembrolizumab. Preclinically, it has been established that chemotherapy resistance can be driven by TLR9 activation and IRAK4 dependent activation of pro-survival NF-kB signaling. Inhibition of IRAK4 has been shown to block this signaling, and to reduce tumor desmoplasia along with revitalization of intratumoral T-cells, setting the stage for combination with immune checkpoint inhibitors. This study is active, but not yet recruiting.

Being presented tomorrow (#2011),

June 5

, is preclinical work from Dr.

Duane Mitchell’s

team at the

University of Florida

, which investigated emavusertib (CA-4948) in melanoma brain metastasis where IRAK4-dependent signaling is known to be high. Emavusertib exposure in the brain and in brain tumors achieved therapeutically relevant levels, resulted in substantial reduction of B16.F10 tumor volume and prolonged survival of the mice.

About Emavusertib (CA-4948)

Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-κB protein complex. Additionally, third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, emavusertib was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS.

About Curis, Inc.

Curis is a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer. In 2015, Curis entered into a collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule antagonists of immune checkpoints including the VISTA/PDL1 antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as the IRAK4 kinase inhibitor, emavusertib (CA-4948). Emavusertib is currently undergoing testing in the Phase 1/2 TakeAim Lymphoma trial, in patients with hematologic malignancies, such as non-

Hodgkins

lymphoma and other B cell malignancies, both as a monotherapy and in combination with BTK inhibitor ibrutinib, and the Phase 1/2 TakeAim Leukemia trial in patients with acute myeloid leukemia and myelodysplastic syndrome, for which it has received Orphan Drug Designation from the U.S. Food and Drug Administration. The FDA has placed a partial clinical hold on the TakeAim Leukemia and TakeAim Lymphoma trials during which no new patients will be enrolled, and current study participants benefiting from treatment may continue to be treated with emavusertib at doses of 300mg BID or lower. In addition, Curis is engaged in a collaboration with ImmuNext for development of CI-8993, a monoclonal anti-VISTA antibody, which is currently undergoing testing in a Phase 1 trial in patients with solid tumors. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge® for the treatment of advanced basal cell carcinoma.

For more information, visit Curis’s website at

www.curis.com

.

Cautionary Note Regarding Forward-Looking Statements:

This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, any statements with respect to Curis’s plans, strategies, objectives or financial results; statements concerning product research, development, clinical trials and studies and commercialization plans, timelines, anticipated results or the therapeutic potential of drug candidates including any statements regarding the initiation, progression, expansion, use, efficacy, dosage and potential benefits of CA-4948 in clinical trials as a monotherapy and/or as a combination therapy, the progression, use and potential benefits of CI-8993, Curis’s plans and timelines to provide preliminary, interim and/or additional data from its ongoing or planned clinical trials, any statements concerning Curis’s expectations regarding its interactions with the FDA or its ability to resolve the partial clinical hold of the TakeAim Leukemia study or the partial clinical hold of the TakeAim Lymphoma study, and statements with respect to mutations or potential biomarkers; and statements of assumptions underlying any of the foregoing.  Forward-looking statements may contain the words “believes,” “expects,” “anticipates,” “plans,” “intends,” “seeks,” “estimates,” “assumes,” “predicts,” “projects,” “targets,” “will,” “may,” “would,” “could,” “should,” “continue,” “potential,” “focus,” “strategy,” “mission,” or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements. For example, the FDA may not remove the partial clinical hold on the Phase 1/2 TakeAim Leukemia trial or the partial clinical hold on the Phase 1/2 TakeAim Lymphoma trial, or may take further regulatory action with regard to such trials; Curis may experience adverse results, delays and/or failures in its drug development programs and may not be able to successfully advance the development of its drug candidates in the time frames it projects, if at all. Curis’s drug candidates may cause unexpected toxicities, fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never achieve the requisite regulatory approvals needed for commercialization. Favorable results seen in preclinical studies and early clinical trials of Curis’s drug candidates may not be replicated in later trials. There can be no guarantee that the collaboration agreements with Aurigene and ImmuNext will continue for their full terms, or the CRADA with NCI, that Curis or its collaborators will each maintain the financial and other resources necessary to continue financing its portion of the research, development and commercialization costs, or that the parties will successfully discover, develop or commercialize drug candidates under the collaboration. Regulatory authorities may determine to delay or restrict Genentech’s and/or Roche’s ability to continue to develop or commercialize Erivedge in BCC. Erivedge may not demonstrate sufficient or any activity to merit its further development in disease indications other than BCC. Competing drugs may be developed that are superior to Erivedge. In connection with its agreement with Oberland Capital, Curis faces risks relating to the transfer and encumbrance of certain royalty and royalty-related payments on commercial sales of Erivedge, including the risk that, in the event of a default by Curis or its wholly-owned subsidiary, Curis could lose all retained rights to future royalty and royalty-related payments, Curis could be required to repurchase such future royalty and royalty-related payments at a price that is a multiple of the payments it has received, and its ability to enter into future arrangements may be inhibited, all of which could have a material adverse effect on its business, financial condition and stock price. Curis will require substantial additional capital to fund its business. If it is not able to obtain sufficient funding, it will be forced to delay, reduce in scope or eliminate some of its research and development programs, including related clinical trials and operating expenses, potentially delaying the time to market for, or preventing the marketing of, any of its product candidates, which could adversely affect its business prospects and its ability to continue operations, and would have a negative impact on its financial condition and its ability to pursue its business strategies. Curis faces substantial competition. Curis and its collaborators face the risk of potential adverse decisions made by the FDA and other regulatory authorities, investigational review boards, and publication review bodies. Curis may not obtain or maintain necessary patent protection and could become involved in expensive and time-consuming patent litigation and interference proceedings. Unstable market and economic conditions, natural disasters, public health crises, political crises and other events outside of Curis’s control could significantly disrupt its operations or the operations of third parties on which Curis depends and could adversely impact Curis’s operating results and its ability to raise capital. For example, the COVID-19 pandemic may result in closures of third-party facilities, impact enrollment in clinical trials or impact sales of Erivedge by Genentech and/or Roche.  The extent to which the COVID-19 pandemic may impact Curis’s business or operating results is uncertain. Other important factors that may cause or contribute to actual results being materially different from those indicated by forward-looking statements include the factors set forth under the captions “Risk Factor Summary” and “Risk Factors” in our most recent Form 10-K and Form 10-Q, and the factors that are discussed in other filings that we periodically make with the Securities and Exchange Commission (“SEC”). In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis’s views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by law.

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